• No results found

The “competition method”, used in the previous chapters, enables the assessment of regional changes in neurotransmitter release. However, this method does not provide information on postsynaptic effects (neuronal activation). Information on neuronal activation can be obtained using [15 O]-H2O or FDG PET, as mentioned previously. In this thesis, we wished to investigate the usefulness of methylphenidate as a dopaminergic probe in such studies. In chapter 6 we studied the effects of this drug on neuronal activation and subjective experiences in healthy volunteers. Previous studies that investigated the effects of dopaminergic drugs on brain activity have mainly used FDG PET (Ernst et al. 1997; London et al. 1990; Volkow et al. 1997b, 1998b, Vollenweider et al. 1998; Wolkin et al. 1987). As mentioned earlier, compared to FDG, the temporal resolution of [15O]-H2O PET is much higher. We were interested in effects of methylphenidate at different time-points, therefore we decided to use [15O]-H2O instead of FDG PET in our study. Scans were made at ten minutes after drug administration, which is the time of the peak in subjective effects, and at 30 minutes after administration, the time of the peak in DA concentration. If methylphenidate is found to induce changes in brain regions that are known to be involved in dopaminergic (dys)function, this method may also be useful to study dopaminergic functional abnormalities in psychiatric patients.


Aalto S, Bruck A, Laine M, Nagren K, Rinne JO (2005). Frontal and temporal dopamine release during working memory and attention tasks in healthy humans: a positron emission tomography study using the high-affinity dopamine D2 receptor ligand [11C]FLB 457. J Neurosci 25:2471-2477.

Anderson IM, Clark L, Elliott R, Kulkarni B, Williams SR, Deakin JF (2002). 5-HT(2C) receptor activation by m-chlorophenylpiperazine detected in humans with fMRI. Neuroreport 13: 1547-1551.

Azmitia EC, Gannon PJ, Kheck NM, Whitaker-Azmitia PM (1996). Cellular localization of the 5-HT1A receptor in primate brain neurons and glial cells.

Neuropsychopharmacology 14: 35-46.

Bantick RA, Deakin JF, Grasby PM (2001). The 5-HT1A receptor in schizophrenia: a promising target for novel atypical neuroleptics? J Psychopharmacol 15: 37-46.

Barnes NM, Sharp T (1999). A review of central 5-HT receptors and their function. Neuropharmacology 38: 1083-1152.

Bhagwagar Z, Rabiner EA, Sargent PA, Grasby PM, Cowen PJ (2004).

Persistent reduction in brain serotonin1A receptor binding in recovered depressed men measured by positron emission tomography with [11C]WAY-100635. Mol Psychiatry 9: 386-392.

Biver F, Wikler D, Lotstra F, Damhaut P, Goldman S, Mendlewicz J (1997).

Serotonin 5-HT2 receptor imaging in major depression: focal changes in orbito-insular cortex. Br J Psychiatry 171: 444-448.

Bloom AS, Hoffmann RG, Fuller SA, Pankiewicz J, Harsch HH, Stein EA (1999). Determination of drug-induced changes in functional MRI signal using a pharmacokinetic model. Hum Brain Mapp 8: 235-244.

Bolla K, Ernst M, Kiehl K, Mouratidis M, Eldreth D, Contoreggi C, Matochik J, Kurian V, Cadet J, Kimes A, Funderburk F, London E (2004). Prefrontal cortical dysfunction in abstinent cocaine abusers. J Neuropsychiatry Clin Neurosci 16:


Brannan T, Prikhojan A, Martinez-Tica J, Yahr MD (1995). In vivo comparison of the effects of inhibition of MAO-A versus MAO-B on striatal L-DOPA and dopamine metabolism. J Neural Transm Park Dis Dement Sect 10:79-89.

Breier A, Su TP, Saunders R, Carson RE, Kolachana BS, de-Bartolomeis A et al (1997). Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. Proc Natl Acad Sci USA 49: 2569-2574.

Brody AL, Saxena S, Silverman DH, Alborzian S, Fairbanks LA, Phelps ME, Huang SC, Wu HM, Maidment K, Baxter LR Jr (1999). Brain metabolic changes in major depressive disorder from pre- to post-treatment with paroxetine.

Psychiatry Res 91: 127-139.

Carson RE, Kiesewetter DO, Jagoda E, Der MG, Herscovitch P, Eckelman WC (1998). Muscarinic cholinergic receptor measurements with [18F]FP-TZTP:

control and competition studies. J Cereb Blood Flow Metab 18: 1130-1142.

Carson RE (2000). PET physiological measurements using constant infusion.

Nucl Med Biol 27: 657-660.

Cook EH Jr, Metz J, Leventhal BL, Lebovitz M, Nathan M, Semerdjian SA, Brown T, Cooper MD (1994). Fluoxetine effects on cerebral glucose metabolism. Neuroreport 5: 1745-1748.

Cools R, Stefanova E, Barker RA, Robbins TW, Owen AM (2002).

Dopaminergic modulation of high-level cognition in Parkinson's disease: the role of the prefrontal cortex revealed by PET. Brain 125: 584-594.

Costes N, Merlet I, Zimmer L, Lavenne F, Cinotti L, Delforge J, Luxen A, Pujol JF, Le-Bars D (2002). Modeling [18 F]MPPF positron emission tomography kinetics for the determination of 5-hydroxytryptamine(1A) receptor concentration with multiinjection. J Cereb Blood Flow Metab 22: 753-765.

De la Fuente Fernandez R, Phillips AG, Zamburlini M, Sossi V, Calne DB, Ruth TJ, Stoessl AJ (2002). Dopamine release in human ventral striatum and expectation of reward. Behav Brain Res 136: 359-363.

De la Fuente Fernandez R, Sossi V, Huang Z, Furtado S, Lu JQ, Calne DB, Ruth TJ, Stoessl AJ (2004). Levodopa-induced changes in synaptic dopamine levels increase with progression of Parkinson's disease: implications for dyskinesias. Brain 127: 2747-2754.

Drevets WC, Frank E, Price JC, Kupfer DJ, Holt D, Greer PJ, Huang Y, Gautier C, Mathis C (1999). PET imaging of serotonin 1A receptor binding in depression. Biol Psychiatry 46: 1375-1387.

Drevets WC, Gautier C, Price JC, Kupfer DJ, Kinahan PE, Grace AA, Price JL, Mathis CA (2001). Amphetamine-induced dopamine release in human ventral striatum correlates with euphoria. Biol Psychiatry 49: 81-96.

Ebert D, Feistel H, Loew T, Pirner A (1996). Dopamine and depression--striatal dopamine D2 receptor SPECT before and after antidepressant therapy.

Psychopharmacology 126: 91-94.

Ernst M, Zametkin AJ, Matochik J, Schmidt M, Jons PH, Liebenauer LL, Hardy KK, Cohen RM (1997). Intravenous dextroamphetamine and brain glucose metabolism. Neuropsychopharmacology 17: 391-401.

Fisher RE, Morris ED, Alpert NM, Fischman AJ (1995). In vivo imaging of neuromodulatory synaptic transmission using PET: A review of relevant neurophysiology. Human Brain Mapping 3: 24-34.

Fletcher PC, Frith CD, Grasby PM, Friston KJ, Dolan RJ (1996). Local and distributed effects of apomorphine on fronto-temporal function in acute unmedicated schizophrenia. J Neurosci 16: 7055-7062.

Floresco SB, West AR, Ash B, Moore H, Grace AA (2003). Afferent modulation of dopamine neuron firing differentially regulates tonic and phasic dopamine transmission. Nat Neurosci 6:968-973.

Fowler JS, Volkow ND, Wang GJ, Ding YS, Dewey SL (1999). PET and drug research and development. J Nucl Med 40: 1154-1163.

Friedman AM, DeJesus OT, Revenaugh J, Dinerstein RJ (1984).

Measurements in vivo of parameters of the dopamine system. Ann Neurol 15 Suppl: S66-76.

Gartside SE, Hajos-Korcsok E, Bagdy E, Harsing LG Jr, Sharp T, Hajos M (2000). Neurochemical and electrophysiological studies on the functional significance of burst firing in serotonergic neurons.

Neuroscience 98:295-300.

Geday J, Hermansen F, Rosenberg R, Smith DF (2005). serotonin modulation of cerebral blood flow measured with positron emission tomography (PET) in humans. Synapse. 2005 Mar 15;55(4):224-9.

Gefvert O, Bergstrom M, Langstrom B, Lundberg T, Lindstrom L, Yates R (1998). Time course of central nervous dopamine-D2 and 5-HT2 receptor blockade and plasma drug concentrations after discontinuation of quetiapine (Seroquel) in patients with schizophrenia. Psychopharmacology 135: 119-126.

Gefvert O, Lundberg T, Wieselgren IM, Bergstrom M, Langstrom B, Wiesel F, Lindstrom L (2001). D(2) and 5HT(2A) receptor occupancy of different doses of quetiapine in schizophrenia: a PET study. Eur Neuropsychopharmacol 11:105-110.

Ginovart N, Hassoun W, Le-Cavorsin M, Veyre L, Le-Bars D, Leviel V (2002).

Effects of amphetamine and evoked dopamine release on [11C]raclopride binding in anesthetized cats. Neuropsychopharmacology 27(1): 72-84.

Ginovart N, Wilson AA, Meyer JH, Hussey D, Houle S (2003). [11C]-DASB, a tool for in vivo measurement of SSRI-induced occupancy of the serotonin transporter: PET characterization and evaluation in cats. Synapse 47: 123-133.

Ginovart N, Sun W, Wilson AA, Houle S Kapur S (2004). Quantitative validation of an intracerebral beta-sensitive microprobe system to determine in vivo drug-induced receptor occupancy using [11C]raclopride in rats. Synapse 52: 89-99.

Goerendt IK, Messa C, Lawrence AD, Grasby PM, Piccini P, Brooks DJ (2003).

Dopamine release during sequential finger movements in health and Parkinson's disease: a PET study. Brain 126: 312-325.

Gozlan H, Thibault S, Laporte AM, Lima L, Hamon M (1995). The selective 5-HT1A antagonist radioligand [3H]WAY 100635 labels both G-protein-coupled and free 5-HT1A receptors in rat brain membranes. Eur J Pharmacol 288: 173-186.

Grunder G, Yokoi F, Offord SJ, Ravert HT, Dannals RF, Salzmann JK, Szymanski S, Wilson PD, Howard DR, Wong DF (1997). Time course of 5-HT2A receptor occupancy in the human brain after a single oral dose of the putative antipsychotic drug MDL 100,907 measured by positron emission tomography. Neuropsychopharmacology 17: 175-185.

Harada N, Ohba H, Fukumoto D, Kakiuchi T, Tsukada H (2004). Potential of [(18)F]beta-CFT-FE (2beta-carbomethoxy-3beta-(4-fluorophenyl)-8-(2-[(18)F]fluoroethyl)nortropane) as a dopamine transporter ligand: A PET study in the conscious monkey brain. Synapse 54(1):37-45.

Hassoun W, Le-Cavorsin M, Ginovart N, Zimmer L, Gualda V, Bonnefoi F, Leviel V (2003). PET study of the [11C]raclopride binding in the striatum of the awake cat: effects of anaesthetics and role of cerebral blood flow. Eur J Nucl Med Mol Imaging 30(1): 141-148.

Herscovitch P (2001). Can [15O]water be used to evaluate drugs? J Clin Pharmacol Suppl: 11S-20S.

Hirani E, Sharp T, Sprakes M, Grasby P, Hume S (2003). Fenfluramine evokes 5-HT2A receptor-mediated responses but does not displace [11C]MDL 100907:

small animal PET and gene expression studies. Synapse 50: 251-260.

Hjorth S, Bengtsson HJ, Kullberg A, Carlzon D, Peilot H, Auerbach SB (2000).

Serotonin autoreceptor function and antidepressant drug action. J Psychopharmacol 14: 177-185.

Holcomb HH, Cascella NG, Thaker GK, Medoff DR, Dannals RF, Tamminga CA (1996). Functional sites of neuroleptic drug action in the human brain: PET/FDG studies with and without haloperidol. Am J Psychiatry 153: 41-49.

Hume S, Hirani E, Opacka-Juffry J, Myers R, Townsend C, Pike V, Grasby P (2001). Effect of 5-HT on binding of [11C] WAY 100635 to 5-HTIA receptors in rat brain, assessed using in vivo microdialysis and PET after fenfluramine.

Synapse 41: 150-159.

Ikemoto S, Glazier BS, Murphy JM, McBride WJ (1997). Role of dopamine D1 and D2 receptors in the nucleus accumbens in mediating reward. J Neurosci 17:8580-8587.

Insel TR, Siever LJ (1981). The dopamine system challenge in affective disorders: a review of behavioral and neuroendocrine responses. J Clin Psychopharmacol 1: 207-213.

Jacobs BL, Azmitia EC (1992). Structure and function of the brain serotonin system. Physiol Rev 72: 165-229.

Jucaite A, Fernell E, Halldin C, Forssberg H, Farde L (2005). Reduced midbrain dopamine transporter binding in male adolescents with attention-deficit/hyperactivity disorder: association between striatal dopamine markers and motor hyperactivity. Biol Psychiatry 57:229-238.

Kaasinen V, Nagren K, Hietala J, Oikonen V, Vilkman H, Farde L, Halldin C, Rinne JO (2000). Extrastriatal dopamine D2 and D3 receptors in early and advanced Parkinson's disease. Neurology 54: 1482-1487.

Kaasinen V, Aalto S, Nagren K, Rinne JO (2004). Expectation of caffeine induces dopaminergic responses in humans. Eur J Neurosci 19: 2352-2356.

Kapur S, Meyer J, Wilson AA, Houle S, Brown GM (1994). Modulation of cortical neuronal activity by a serotonergic agent: a PET study in humans. Brain Res 646: 292-294.

Kapur S, Seeman P (2001). Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics?: A new hypothesis. Am J Psychiatry 158: 360-369.

Kapur S, Mamo D (2003). Half a century of antipsychotics and still a central role for dopamine D2 receptors. Prog Neuropsychopharmacol Biol Psychiatry 27:


Karhunen T, Tilgmann C, Ulmanen I, Panula P (1995). Catechol-O-methyltransferase (COMT) in rat brain: immunoelectron microscopic study with an antiserum against rat recombinant COMT protein. Neurosci Lett 187:57-60.

Kegeles LS, Malone KM, Slifstein M, Ellis SP, Xanthopoulos E, Keilp JG, Campbell C, Oquendo M, Van-Heertum RL, Mann JJ (2003). Response of cortical metabolic deficits to serotonergic challenge in familial mood disorders.

Am J Psychiatry 160: 76-82.

Kenakin T (2002). Efficacy at G-protein-coupled receptors. Nat Rev Drug Discov 1: 103-110.

Khawaja X (1995). Quantitative autoradiographic characterisation of the binding of [3H]WAY-100635, a selective 5-HT1A receptor antagonist. Brain Res 673:


Klimke A, Larisch R, Janz A, Vosberg H, Muller-Gartner HW, Gaebel W (1999).

Dopamine D2 receptor binding before and after treatment of major depression measured by [123I]IBZM SPECT. Psychiatry Res 90: 91-101.

Koepp MJ, Gunn RN, Lawrence AD, Cunningham VJ, Dagher A, Jones T, Brooks DJ, Bench CJ, Grasby PM (1998a). Evidence for striatal dopamine release during a video game. Nature 393: 266-268.

Koepp MJ, Richardson MP, Brooks DJ, Duncan JS (1998b). Focal cortical release of endogenous opioids during reading-induced seizures. Lancet 352:


Kohler C, Hall H, Ogren SO, Gawell L (1985). Specific in vitro and in vivo binding of 3H-raclopride. A potent substituted benzamide drug with high affinity for dopamine D-2 receptors in the rat brain. Biochem Pharmacol 34: 2251-2259.

Lahti AC, Holcomb HH, Weiler MA, Medoff DR, Frey KN, Hardin M, Tamminga CA (2004). Clozapine but not haloperidol Re-establishes normal task-activated rCBF patterns in schizophrenia within the anterior cingulate cortex.

Neuropsychopharmacology 29: 171-178.

Laihinen AO, Rinne JO, Nagren KA, Lehikoinen PK, Oikonen VJ, Ruotsalainen UH, Ruottinen HM, Rinne UK (1995). PET studies on brain monoamine transporters with carbon-11-beta-CIT in Parkinson's disease. J Nucl Med 36:


Laruelle M, Abi-Dargham A, van-Dyck CH, Rosenblatt W, Zea-Ponce Y, Zoghbi SS, Baldwin RM, Charney DS, Hoffer PB, Kung HF, Innis RB (1995). SPECT imaging of striatal dopamine release after amphetamine challenge. J Nucl Med 36: 1182-1190.

Laruelle M, Iyer RN, al-Tikriti MS, Zea-Ponce Y, Malison R, Zoghbi SS, Baldwin RM, Kung HF, Charney DS, Hoffer PB, Innis RB, Bradberry CW (1997).

Microdialysis and SPECT measurements of amphetamine-induced dopamine release in nonhuman primates. Synapse 25: 1-14.

Laruelle M (2000). Imaging synaptic neurotransmission with in vivo binding competition techniques: a critical review. J Cereb Blood Flow Metab 20: 423-451.

Laruelle M, Slifstein M, Huang Y (2003). Relationships between radiotracer properties and image quality in molecular imaging of the brain with positron emission tomography. Mol Imaging Biol 5: 363-375.

Learned-Coughlin SM, Bergstrom M, Savitcheva I, Ascher J, Schmith VD, Langstrom B (2003). In vivo activity of bupropion at the human dopamine transporter as measured by positron emission tomography. Biol Psychiatry 54:


Leenders KL (2002). Disease process and drug treatments in Parkinson's disease. Eur Neuropsychopharmacol 12: 575-580.

Lefkowitz RJ, Cotecchia S, Samama P, Costa T (1993). Constitutive activity of receptors coupled to guanine nucleotide regulatory proteins. Trends Pharmacol Sci 14: 303-307.

Le-Moal M, Simon H (1991). Mesocorticolimbic dopaminergic network:

functional and regulatory roles. Physiol Rev 71: 155-234.

Leyton M, Boileau I, Benkelfat C, Diksic M, Baker G, Dagher A (2002).

Amphetamine-induced increases in extracellular dopamine, drug wanting, and novelty seeking: a PET/[11C]raclopride study in healthy men.

Neuropsychopharmacology 27: 1027-1035.

London ED, Cascella NG, Wong DF, Phillips RL, Dannals RF, Links JM, Herning R, Grayson R, Jaffe JH, Wagner HN Jr (1990). Cocaine-induced reduction of glucose utilization in human brain. A study using positron emission tomography and [fluorine 18]-fluorodeoxyglucose. Arch Gen Psychiatry 47: 567-574.

Loo H, Dalery J, Macher JP, Payen A (2003). Pilot study comparing in blind the therapeutic effect of two doses of agomelatine, melatonin- agonist and selective 5HT2c receptors antagonist, in the treatment of major depressive disorders.

Encephale 29:165-171.

Lundberg T, Lindstrom LH, Hartvig P, Eckernas SA, Ekblom B, Lundqvist H, Fasth KJ, Gullberg P, Langstrom B (1989). Striatal and frontal cortex binding of 11-C-labelled clozapine visualized by positron emission tomography (PET) in drug-free schizophrenics and healthy volunteers. Psychopharmacology 99: 8-12.

Maeda J, Suhara T, Ogawa M, Okauchi T, Kawabe K, Zhang MR, Semba J, Suzuki K (2001). In vivo binding properties of [carbonyl-11C]WAY-100635: effect of endogenous serotonin. Synapse 40: 122-129.

Majovski LV, Jacques S, Hartz G, Fogwell LA (1981). Dopaminergic (DA) systems: their role in pathological neurobehavioral symptoms. Neurosurgery 9:751-757.

Mann JJ, Malone KM, Diehl DJ, Perel J, Nichols TE, Mintun MA (1996).

Positron emission tomographic imaging of serotonin activation effects on prefrontal cortex in healthy volunteers. J Cereb Blood Flow Metab 16: 418-426.

Martinez D, Hwang D, Mawlawi O, Slifstein M, Kent J, Simpson N, Parsey RV, Hashimoto T, Huang Y, Shinn A, Van-Heertum R, Abi-Dargham A, Caltabiano S, Malizia A, Cowley H, Mann JJ, Laruelle M (2001). Differential occupancy of somatodendritic and postsynaptic 5HT(1A) receptors by pindolol: a dose-occupancy study with [11C]WAY 100635 and positron emission tomography in humans. Neuropsychopharmacology 24: 209-229.

Martinez D, Slifstein M, Broft A, Mawlawi O, Hwang DR, Huang Y, Cooper T, Kegeles L, Zarahn E, Abi-Dargham A, Haber SN, Laruelle M (2003). Imaging human mesolimbic dopamine transmission with positron emission tomography.

Part II: amphetamine-induced dopamine release in the functional subdivisions of the striatum. J Cereb Blood Flow Metab 23: 285-300.

Martinez D, Broft A, Foltin RW, Slifstein M, Hwang DR, Huang Y, Perez A, Frankle WG, Cooper T, Kleber HD, Fischman MW, Laruelle M (2004). Cocaine dependence and d2 receptor availability in the functional subdivisions of the striatum: relationship with cocaine-seeking behavior.

Neuropsychopharmacology 29: 1190-1202.

Massou JM, Trichard C, Attar-Levy D, Feline A, Corruble E, Beaufils B, Martinot JL (1997). Frontal 5-HT2A receptors studied in depressive patients during chronic treatment by selective serotonin reuptake inhibitors.

Psychopharmacology 133: 99-101.

Mayberg HS, Brannan SK, Tekell JL, Silva JA, Mahurin RK, McGinnis S, Jerabek PA (2000). Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response. Biol Psychiatry 48: 830-843.

Meltzer CC, Price JC, Mathis CA, Butters MA, Ziolko SK, Moses-Kolko E, Mazumdar S, Mulsant BH, Houck PR, Lopresti BJ, Weissfeld LA, Reynolds CF (2004). Serotonin 1A receptor binding and treatment response in late-life depression. Neuropsychopharmacology 29: 2258-2265.

Messa C, Colombo C, Moresco RM, Gobbo C, Galli L, Lucignani G, Gilardi MC, Rizzo G, Smeraldi E, Zanardi R, Artigas F, Fazio F (2003). 5-HT(2A) receptor binding is reduced in drug-naive and unchanged in SSRI-responder depressed patients compared to healthy controls: a PET study. Psychopharmacology 167:


Meyer JH, Kapur S, Wilson AA, DaSilva JN, Houle S, Brown GM (1996).

Neuromodulation of frontal and temporal cortex by intravenous d-fenfluramine:

an [15O]H2O PET study in humans. Neurosci Lett 207: 25-28.

Meyer JH, Cho R, Kennedy S, Kapur S (1999). The effects of single dose nefazodone and paroxetine upon 5-HT2A binding potential in humans using [18F]-setoperone PET. Psychopharmacology 144: 279-281.

Meyer JH, Swinson R, Kennedy SH, Houle S, Brown GM (2000). Increased left posterior parietal-temporal cortex activation after D-fenfluramine in women with panic disorder. Psychiatry Res 98: 133-143.

Meyer JH, Kapur S, Eisfeld B, Brown GM, Houle S, DaSilva J, Wilson AA, Rafi-Tari S, Mayberg HS, Kennedy SH (2001a). The effect of paroxetine on 5-HT(2A) receptors in depression: an [(18)F]setoperone PET imaging study. Am J Psychiatry 158: 78-85.

Meyer JH, Wilson AA, Ginovart N, Goulding V, Hussey D, Hood K, Houle S (2001b). Occupancy of serotonin transporters by paroxetine and citalopram during treatment of depression: a [(11)C]DASB PET imaging study. Am J Psychiatry 158: 1843-1849.

Meyer JH, McMain S, Kennedy SH, Korman L, Brown GM, DaSilva JN, Wilson AA, Blak T, Eynan-Harvey R, Goulding VS, Houle S, Links P (2003).

Dysfunctional attitudes and 5-HT2 receptors during depression and self-harm.

Am J Psychiatry 160:90-99.

Meyer JH, Houle S, Sagrati S, Carella A, Hussey DF, Ginovart N, Goulding V, Kennedy J, Wilson AA (2004). Brain serotonin transporter binding potential measured with carbon 11-labeled DASB positron emission tomography: effects of major depressive episodes and severity of dysfunctional attitudes. Arch Gen Psychiatry 61: 1271-1279.

Miller DD, Andreasen NC, O'Leary DS, Rezai K, Watkins GL, Ponto LL, Hichwa RD (1997). Effect of antipsychotics on regional cerebral blood flow measured with positron emission tomography. Neuropsychopharmacology 17: 230-240.

Mintun MA, Raichle ME, Kilbourn MR, Wooten GF, Welch MJ (1984). A quantitative model for the in vivo assessment of drug binding sites with positron emission tomography. Ann Neurol 15: 217-227.

Momosaki S, Hatano K, Kawasumi Y, Kato T, Hosoi R, Kobayashi K, Inoue O, Ito K (2004). Rat-PET study without anesthesia: Anesthetics modify the dopamine D(1) receptor binding in rat brain. Synapse 54(4): 207-213.

Mongeau R, Welner SA, Quirion R, Suranyi-Cadotte BE (1992). Further evidence for differential affinity states of the serotonin1A receptor in rat hippocampus. Brain Res 590: 229-238.

Naranjo CA, Tremblay LK, Busto UE (2001). The role of the brain reward system in depression. Prog Neuropsychopharmacol Biol Psychiatry 25: 781-823.

Nénonéné EK, Radja F, Carli M, Grondin L, Reader TA (1994). Heterogeneity of cortical and hippocampal 5-HT1A receptors: a reappraisal of homogenate binding with 8-[3H]hydroxydipropylaminotetralin. J Neurochem 62: 1822-1834.

Neumeister A, Bain E, Nugent AC, Carson RE, Bonne O, Luckenbaugh DA, Eckelman W, Herscovitch P, Charney DS, Drevets WC (2004).Reduced serotonin type 1A receptor binding in panic disorder. J Neurosci 24:589-591.

Nishiyama S, Tsukada H, Sato K, Kakiuchi T, Ohba H, Harada N, Takahashi K (2001). Evaluation of PET ligands (+)N-[11C]ethyl-3-piperidyl benzilate and (+)N-[11C]propyl-3-piperidyl benzilate for muscarinic cholinergic receptors: A PET study with microdialysis in comparison with (+)N-[11C]methyl-3-piperidyl benzilate in the conscious monkey brain. Synapse 40: 159-169.

Nordstrom AL, Farde L, Halldin C (1992). Time course of D2-dopamine receptor occupancy examined by PET after single oral doses of haloperidol.

Psychopharmacology 106: 433-438.

Nurmi E, Ruottinen HM, Kaasinen V, Bergman J, Haaparanta M, Solin O, Rinne JO (2000). Progression in Parkinson's disease: a positron emission tomography study with a dopamine transporter ligand [18F]CFT. Ann Neurol 47: 804-808.

Nyberg S, Nilsson U, Okubo Y, Halldin C, Farde L (1998). Implications of brain imaging for the management of schizophrenia. Int Clin Psychopharmacol 13 Suppl 3: S15-20.

Nyberg S, Farde L (2000). Non-equipotent doses partly explain differences among antipsychotics - implications of PET studies. Psychopharmacology 148:


Oosterink BJ, Korte SM, Nyakas C, Korf J, Luiten PG (1998). Neuroprotection against N-methyl-D-aspartate-induced excitotoxicity in rat magnocellular nucleus basalis by the 5-HT1A receptor agonist 8-OH-DPAT. Eur J Pharmacol 358: 147-152.

Oquendo M A, Placidi GP, Malone KM, Campbell C, Keilp J, Brodsky B, Kegeles LS, Cooper TB, Parsey RV, van-Heertum RL, Mann JJ (2003).

Positron emission tomography of regional brain metabolic responses to a serotonergic challenge and lethality of suicide attempts in major depression.

Arch Gen Psychiatry 60: 14-22.

Paterson IA, Davis BA, Durden DA, Juorio AV, Yu PH, Ivy G, Milgram W, Mendonca A, Wu P, Boulton AA (1995). Inhibition of MAO-B by (-)-deprenyl alters dopamine metabolism in the macaque (Macaca facicularis) brain.

Neurochem Res 20:1503-1510.

Perani D, Colombo C, Bressi S, Bonfanti A, Grassi F, Scarone S, Bellodi L, Smeraldi E, Fazio F (1995). [18F]FDG PET study in obsessive-compulsive disorder. A clinical/metabolic correlation study after treatment. Br J Psychiatry 166: 244-250.

Pinborg LH, Adams KH, Yndgaard S, Hasselbalch SG, Holm S, Kristiansen H, Paulson OB, Knudsen GM (2004). [18F]altanserin binding to human 5HT2A receptors is unaltered after citalopram and pindolol challenge. J Cereb Blood Flow Metab 24: 1037-1045.

Pineyro G, Blier P (1999). Autoregulation of serotonin neurons: role in antidepressant drug action.

Pharmacol Rev 51:533-591. Review.

Power AC, Cowen PJ (1992). Neuroendocrine challenge tests: assessment of 5-HT function in anxiety and depression. Mol Aspects Med 13: 205-220.

Pruessner JC, Champagne F, Meaney MJ, Dagher A (2004). Dopamine release in response to a psychological stress in humans and its relationship to early life maternal care: a positron emission tomography study using [11C]raclopride. J Neurosci 24: 2825-2831.

Rabiner EA, Bhagwagar Z, Gunn RN, Sargent PA, Bench CJ, Cowen PJ, Grasby PM (2001). Pindolol augmentation of selective serotonin reuptake

Rabiner EA, Bhagwagar Z, Gunn RN, Sargent PA, Bench CJ, Cowen PJ, Grasby PM (2001). Pindolol augmentation of selective serotonin reuptake